Transcranial direct current stimulation for pain threshold in knee osteoarthritis: a mechanism-oriented systematic review and meta-analysis of randomized controlled trials

Background Knee osteoarthritis (KOA) pain is increasingly recognized to involve altered central pain processing, including central sensitization and impaired descending inhibitory pathways. Transcranial direct current stimulation (tDCS) may alleviate pain by modulating cortical excitability and pain-related networks. However, evidence on pain threshold remains fragmented. Objective To systematically evaluate the effects of tDCS on pain threshold in patients with KOA, and to assess its effects on pain intensity, physical function, walking capacity, and safety. Methods This systematic review and meta-analysis followed PRISMA 2020. MEDLINE, Embase, Cochrane Library, and Web of Science were searched from inception to October 7, 2025 for randomized controlled trials (RCTs) involving patients with KOA. Primary outcomes consisted of pain thresholds that reflect pain sensitivity, namely pressure pain threshold (PPT), conditioned pain modulation (CPM), heat pain threshold (HPTh), and heat pain tolerance (HPTo). Secondary outcomes included pain intensity (VAS/NRS), physical function (WOMAC/KOOS), and walking capacity (6MWT/10MWT). Risk of bias was assessed using RoB 2.0. Results Seventeen RCTs involving 1,113 participants were included. Compared with controls, tDCS significantly improved pain threshold overall (SMD = 0.55, 95% CI: 0.32 to 0.78; P < 0.01; I² = 66.2%). Subgroup analyses showed significant improvements in CPM (SMD = 0.47, 95% CI: 0.18 to 0.77), HPTo (SMD = 0.40, 95% CI: 0.09 to 0.71), and PPT (SMD = 0.77, 95% CI: 0.25 to 1.30), whereas HPTh did not differ significantly from controls. tDCS also significantly reduced pain intensity (SMD = -0.65, 95% CI: -0.91 to -0.39; P < 0.01; I² = 67.3%). Physical function was improved (SMD = -0.38, 95% CI: -0.54 to -0.21, P < 0.01; I² = 0.0%). Risk of bias was rated as low in 9 studies, some concerns in 7 studies, and high in 1 study. Adverse events were generally mild and transient, with no serious intervention-related adverse events reported. Conclusions Current evidence suggests that tDCS may improve pain threshold and reduce pain intensity in patients with KOA. However, the effects on physical function remain less certain because of substantial heterogeneity and potential risk-of-bias effects. Future high-quality RCTs with mechanistic stratification and standardized stimulation and assessment protocols are warranted. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php? , identifier CRD420261297687.